Pertussis, or whooping cough, is an infection of the respiratory tract caused by the Gram-negative bacterium Bordetella pertussis. Pertussis infections are directly transmitted through the air and can cause respiratory complications (e.g., uncontrollable, violent coughing), nerve damage and high mortality, particularly in children of low socio-economic groups and in new born babies without maternal, anti-pertussis antibodies. Infants with pertussis often require hospitalization in pediatric intensive care units, and their treatments involve mechanical ventilation. Pertussis in adults generally leads to a chronic cough referred to as the “cough of 100 days.”
While antibiotic treatment can eliminate the B. pertussis bacteria from the respiratory tract, it does not neutralize the pertussis toxin (PT) protein, which is a major contributor to disease and is responsible for local and systemic disease symptoms including leukocytosis and immunosuppression. As such, antibiotic treatments often have minimal effects on the course of pertussis. In contrast, antibody therapy offers the advantage of specificity that antibiotic treatments may lack.
Antibodies that bind the pertussis toxin protein have been developed. In addition, antibody cocktails comprising different antibodies that bind the pertussis toxin protein have also been developed. However, such antibody cocktails and mixtures have the drawbacks of increased complexity and costs of manufacturing. For example, a binary mixture typically involves production and manufacturing of each antibody separately, with a final mixing step prior to fill/finish processing. Such methods are also susceptible to batch failure from each individual antibody. Additionally, antibody mixtures are subject to the same strict FDA approval processes as monoclonal preparations, and documentation for the safety of each individual component as well as the mixture is needed.
Accordingly, there remains a need for improved antibody-based agents against the pertussis toxin protein with increased efficacy and reduced side effects and which can be easily manufactured.